The objective of this research project is to investigate the pharmacokinetic functions of the lung with regard to both endogenous and exogenous chemicals. An isolated perfused lung (IPL) system has been developed, which permits examination of the pharmacokinetics of chemicals reaching the lung both from the circulation and from the inhaled air. Pharmacokinetic data will be correlated with toxicological, physiological, and biochemical changes induced during the accumulation of pollutants by the lung. Pharmacokinetic models will be constructed and related to environmentally induced pulmonary damage. The role of the lung in the whole body disposition of environmental agents will be assessed and data will be incorporated into pharmacokinetic models for the uptake and disposition of chemicals by the lung.